Topotecan Hydrochloride or Cyclodextrin-Based Polymer-Camptothecin CRLX101 in Treating Patients With Recurrent Small Cell Lung Cancer

PRIMARY OBJECTIVES:

I. To evaluate the effect of second-line treatment with CRLX101 (cyclodextrin-based
polymer-camptothecin CRLX101) compared to intravenous (IV) topotecan hydrochloride
(topotecan) on progression free survival (PFS) of patients with extensive-stage small cell
lung cancer (ES-SCLC) sensitive to first-line platinum-based chemotherapy.

II. To evaluate the effect of second-line treatment with CRLX101 on the three-month PFS rate
of patients with ES-SCLC resistant to first-line platinum-based chemotherapy.

SECONDARY OBJECTIVES:

I. To evaluate the response rate of second-line treatment with CRLX101 in patients with
ES-SCLC who are sensitive or resistant to first-line platinum-based chemotherapy.

II. To evaluate the effect of second-line treatment with CRLX101 compared to IV topotecan on
overall survival (OS) of patients with ES-SCLC sensitive to first-line platinum-based
chemotherapy.

III. To assess the overall survival of second-line treatment with CRLX101 in patients with
ES-SCLC resistant to first-line platinum-based chemotherapy.

IV. To assess the toxicity of second-line CRLX101 in patients sensitive or resistant to
first-line platinum-based chemotherapy.

OUTLINE: Patients are assigned to 1 of 2 cohorts.

COHORT A (Sensitive Relapse): Patients are randomized to 1 of 2 treatment arms.

ARM A: Patients receive topotecan hydrochloride intravenously (IV) over 30 minutes on days
1-5. Courses repeat every 21 days in the absence of disease progression or unacceptable
toxicity.

ARM B: Patients receive cyclodextrin-based polymer-camptothecin CRLX101 IV over 60 minutes on
days 1 and 15. Courses repeat every 28 days in the absence of disease progression or
unacceptable toxicity.

COHORT B (Resistant Relapse): Patients receive cyclodextrin-based polymer-camptothecin
CRLX101 as in Arm B Cohort A. Courses repeat every 28 days in the absence of disease
progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 4 weeks and then every 3
months thereafter.

Inclusion Criteria:

- Patients must have histologically or cytologically confirmed small cell lung cancer

- All patients must have extensive stage disease; extensive stage patients are
defined as those patients with bilateral or contralateral supraclavicular
adenopathy or contralateral hilar adenopathy or malignant pleural effusion or
extrathoracic metastatic disease

- Patients must have measurable disease, defined as at least one lesion that can be
accurately measured in at least one dimension (longest diameter to be recorded for
non-nodal lesions and short axis for nodal lesions) as >= 20 mm with conventional
techniques or as >= 10 mm with spiral computed tomography (CT) scan, magnetic
resonance imaging (MRI), or calipers by clinical exam

- Patients must have been treated with 1 prior platinum-based (cisplatin or carboplatin)
regimen; prior thoracic radiation for limited stage disease is allowed; patients must
be at least 4 weeks since prior chemotherapy or radiation

- Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)

- Life expectancy of greater than 3 months

- Leukocytes >= 3,000/mcL

- Absolute neutrophil count >= 1,500/mcL

- Platelets >= 100,000/mcL

- Total bilirubin within normal institutional limits

- Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
=< 2.5 x institutional upper limit of normal

- Creatinine within normal institutional limits OR

- Creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above
institutional normal

- Baseline imaging studies performed =< 28 days of study registration

- The effects of CRLX101 on the developing human fetus are unknown; women of
child-bearing potential and men must agree to use adequate contraception (hormonal or
barrier method of birth control; abstinence) prior to study entry and for the duration
of study participation; should a woman become pregnant or suspect she is pregnant
while she or her partner is participating in this study, she should inform her
treating physician immediately; men treated or enrolled on this protocol must also
agree to use adequate contraception prior to the study, for the duration of study
participation, and 4 months after completion of CRLX101 administration

- Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

- Patients who have had chemotherapy or radiotherapy within 2 weeks to entering the
study or those who have not recovered from adverse events due to agents administered
more than 4 weeks earlier

- Patients who have previously been treated with irinotecan or topotecan

- Patients who are receiving any other investigational agents

- Patients with uncontrolled brain metastases; patients with treated brain metastases
must have stable neurologic status off of steroids and anticonvulsants for at least 2
weeks and must be without neurologic dysfunction that would confound the evaluation of
neurologic and other adverse events

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to CRLX101 or topotecan

- Patients with uncontrolled intercurrent illness including, but not limited to ongoing
or active infection, symptomatic congestive heart failure, unstable angina pectoris,
cardiac arrhythmia, or psychiatric illness/social situations that would limit
compliance with study requirements

- Previous or concurrent malignancy; exceptions: treated basal cell or squamous cell
skin cancer, in situ cervical cancer, or lobular carcinoma in situ in one breast; or
other cancer which the patient has been disease-free >= 5 years

- Pregnant women and women who are capable of reproduction but who will not agree to use
adequate contraception prior to study entry and for the duration of study
participation; because there is an unknown but potential risk for adverse events in
nursing infants secondary to treatment of the mother with CRLX101 or topotecan,
breastfeeding should be discontinued if the mother is treated with either agent

- Human immunodeficiency virus (HIV)-positive patients

- Patients with history of inflammatory bowel disease requiring therapy or patients with
chronic diarrhea syndromes or paralytic ileus